1. Field of the Invention
The invention relates generally to .sup.18 F labeling of organic compounds and, more particularly, to a process for the production of .sup.18 F-labeled organic compounds by nucleophilic exchange.
2. Description of the Prior Art
The production of compounds labeled with fluorine-18 has for years been the focus of radiopharmaceutical research for nuclear medicine and functional diagnosis. This is because of the optimal nuclear properties of fluorine-18 for positron emission tomography (PET). The positron emitter, fluorine-18, is more advantageous to use in many applications than other radionuclides, as a means by which covalently-bonded fluorine compounds can be labeled. Fluorine-18, because of its decay energy (0.64 MeV), allows the highest inherent resolution during PET measurements (without interfering secondry lines). In addition, fluorine-18 has a relatively convenient half life, T.sub.1/2, of 109.7 minutes.
Carrier-free or labeled compounds of extremely high specific activity of more than 1000 curies/mmol are especially necessary for in vivo receptor studies, and in all cases where, for toxicological reasons or not to disturb sensitive biological equilibria, an in vivo application in the subnanomolar or picomolar region is necessary. Electrophilic processes have all recently been based on labeled molecular fluorine (F.sub.2). However, the molecular fluorine inherently contains inactive fluorine carriers with the resultant problems ensuing therefrom. The nucleophilic substitution with fluoride essentially makes possible an introduction of .sup.18 F without or if any only extremely small quantities of carrier substances. The problems of reactions with fluoride lie in its extremely high charge density and hydrophilic properties, which cause a weak nucleophilic action and high adsorption losses, especially when working without a carrier additive. Reactions which utilize carrier-free fluoride therefore generally require the careful exclusion of water.
Previous investigations have attempted to increase the reactivity of ammonium or alkali fluorides by the addition of phase transfer catalyst, such as long-chain onium salts and cyclic polyethers (crown ethers), or by the addition of silver oxide, as well as by the use of easily-substitutable leaving groups such as tosylates and triflates. Except for a few cases, production without the addition of carriers was so far possible only with simple alkyl compounds, and even then produced only small yields (less than 20%). Higher yields were obtained only with fluoroethanol, methyl fluoride and simple aromatic molecules, substituted benzols, with the latter by the replacement of the nitro-group in DMSO, at relatively high temperatures of 150.degree. C. with Rb.sup.18 F. DMSO is dimethyl sulfoxide, which is described in U.S. Pat. No. 4,514,377, which patent is incorporated herein by reference.